PMID- 36350155 OWN - NLM STAT- MEDLINE DCOM- 20230215 LR - 20230215 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 38 IP - 2 DP - 2023 Feb TI - Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-kappaB signaling pathway. PG - 253-265 LID - 10.1002/tox.23699 [doi] AB - BACKGROUND: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential. MATERIAL/METHODS: In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of beta-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-kappaB (NF-kappaB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4(+) IFN-gamma(+) ) / Th2 (CD4(+) IL-4(+) ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry. RESULTS: Apigenin significantly inhibited compound 48/80-induced secretion of beta-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-kappaB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as beta-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice. CONCLUSIONS: Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-kappaB signaling pathway. CI - (c) 2022 Wiley Periodicals LLC. FAU - Li, Huajing AU - Li H AD - Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Zhang, Hongmei AU - Zhang H AD - Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Zhao, Hua AU - Zhao H AUID- ORCID: 0000-0002-4627-247X AD - Department of Pharmacy, Affiliated Hospital of Medical College of Xi'an Jiaotong University, Shaanxi Provincial Cancer Hospital, Xi'an, China. LA - eng GR - The Basic research plan of Natural Science in Shaanxi Province (2020JM-382) in China/ PT - Journal Article DEP - 20221109 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 7V515PI7F6 (Apigenin) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) RN - 0 (Cytokines) RN - 820484N8I3 (Histamine) RN - 37341-29-0 (Immunoglobulin E) RN - 0 (Immunoglobulin G) RN - 207137-56-2 (Interleukin-4) RN - 0 (Lipopolysaccharides) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 9006-59-1 (Ovalbumin) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Animals MH - Mice MH - *Apigenin/pharmacology/therapeutic use MH - beta-N-Acetylhexosaminidases/metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Histamine/toxicity MH - Immunoglobulin E MH - Immunoglobulin G/toxicity/metabolism MH - Interleukin-4 MH - Leukocytes, Mononuclear/metabolism MH - Lipopolysaccharides/pharmacology MH - Mice, Inbred BALB C MH - *Myeloid Differentiation Factor 88/metabolism MH - *NF-kappa B/metabolism MH - Ovalbumin/pharmacology MH - *Rhinitis, Allergic/chemically induced/drug therapy MH - Signal Transduction MH - Th2 Cells MH - *Toll-Like Receptor 4/metabolism OTO - NOTNLM OT - HMC-1 mast cells OT - TLR4/MyD88/NF-kappaB pathway OT - allergic rhinitis OT - apigenin OT - inflammatory response EDAT- 2022/11/10 06:00 MHDA- 2023/01/18 06:00 CRDT- 2022/11/09 09:04 PHST- 2022/10/10 00:00 [revised] PHST- 2021/08/03 00:00 [received] PHST- 2022/10/13 00:00 [accepted] PHST- 2022/11/10 06:00 [pubmed] PHST- 2023/01/18 06:00 [medline] PHST- 2022/11/09 09:04 [entrez] AID - 10.1002/tox.23699 [doi] PST - ppublish SO - Environ Toxicol. 2023 Feb;38(2):253-265. doi: 10.1002/tox.23699. Epub 2022 Nov 9.